Meloidogyne graminicola Population Structure in China Suggests a South-to-North Expansion.

The distribution range of root-knot nematode Meloidogyne graminicola is rapidly expanding, posing a severe threat to rice production. In this study, the sequences of cytochrome oxidase subunit I (COI) genes of rice M. graminicola populations from all reported provinces in China were amplified and sequenced by PCR. The distribution pattern and phylogenetic tree showed that all 54 M. graminicola populations in China have distinct geographical distribution characteristics; specifically, cluster 1 (southern China), cluster 2 (central south and southwest China), and cluster 3 (central and eastern China). The high haplotype diversity (Hd = 0.646) and low nucleotide diversity (π = 0.00682), combined with the negative value of Tajima's D (-1.252) and Fu's Fs (-3.06764), suggested that all nematode populations were expanding. The existence of high genetic differentiation (Fst = 0.5933) and low gene flow (Nm = 0.3333) indicated that there was a block of gene exchange between most populations. Mutation accumulation with population expansion might be directly responsible for the high genetic differentiation; therefore, the tested nematode population showed high within-group genetic variation (96.30%). The haplotype Hap8 was located at the bottom of the network topology, with the widest distribution and the highest frequency (59.26%), indicating that it was the ancestral haplotype. The populations in cluster 3 were newly invasive according to the lowest frequency of occurrence of Hap8, the highest number of endemic haplotypes, and the highest total haplotype frequency (60%). In contrast, cluster 1 having the highest genetic diversity (Hd = 0.772, π = 0.01127) indicated that it was the most primitive. Interestingly, the highest gene flow (Nm > 1), lowest genetic differentiation (Fst ≤ 0.33), and closest genetic distance (0.000) only occurred between the Guangdong/Hainan population and others, which suggested that there might be channels for gene exchange between them and that long-distance dispersal occurred. This suggestion is further confirmed by the weak correlation between genetic distance and geographical distance. Based on these data, a hypothesis can be drawn that M. graminicola populations in China were spreading from south to north, specifically from Guangdong and Hainan Provinces to other regions. Natural selection (including anthropogenic) and genetic drift were the main drivers of their evolution. Coincidentally, this hypothesis was consistent with the gradual warming trend and the chronological order of reporting these populations. The main factors influencing current M. graminicola population expansion and distribution patterns might be geography, climate, long-distance seedling transport, interregional operations of agricultural machinery, and rotation mode. It reminds human beings of the necessity to be vigilant about preventing nematode disease according to local conditions all year round.

Detection of Pathogenic Variants With Germline Genetic Testing Using Deep Learning vs Standard Methods in Patients With Prostate Cancer and Melanoma.

Importance: Less than 10% of patients with cancer have detectable pathogenic germline alterations, which may be partially due to incomplete pathogenic variant detection. Objective: To evaluate if deep learning approaches identify more germline pathogenic variants in patients with cancer. Design, Setting, and Participants: A cross-sectional study of a standard germline detection method and a deep learning method in 2 convenience cohorts with prostate cancer and melanoma enrolled in the US and Europe between 2010 and 2017. The final date of clinical data collection was December 2017. Exposures: Germline variant detection using standard or deep learning methods. Main Outcomes and Measures: The primary outcomes included pathogenic variant detection performance in 118 cancer-predisposition genes estimated as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The secondary outcomes were pathogenic variant detection performance in 59 genes deemed actionable by the American College of Medical Genetics and Genomics (ACMG) and 5197 clinically relevant mendelian genes. True sensitivity and true specificity could not be calculated due to lack of a criterion reference standard, but were estimated as the proportion of true-positive variants and true-negative variants, respectively, identified by each method in a reference variant set that consisted of all variants judged to be valid from either approach. Results: The prostate cancer cohort included 1072 men (mean [SD] age at diagnosis, 63.7 [7.9] years; 857 [79.9%] with European ancestry) and the melanoma cohort included 1295 patients (mean [SD] age at diagnosis, 59.8 [15.6] years; 488 [37.7%] women; 1060 [81.9%] with European ancestry). The deep learning method identified more patients with pathogenic variants in cancer-predisposition genes than the standard method (prostate cancer: 198 vs 182; melanoma: 93 vs 74); sensitivity (prostate cancer: 94.7% vs 87.1% [difference, 7.6%; 95% CI, 2.2% to 13.1%]; melanoma: 74.4% vs 59.2% [difference, 15.2%; 95% CI, 3.7% to 26.7%]), specificity (prostate cancer: 64.0% vs 36.0% [difference, 28.0%; 95% CI, 1.4% to 54.6%]; melanoma: 63.4% vs 36.6% [difference, 26.8%; 95% CI, 17.6% to 35.9%]), PPV (prostate cancer: 95.7% vs 91.9% [difference, 3.8%; 95% CI, -1.0% to 8.4%]; melanoma: 54.4% vs 35.4% [difference, 19.0%; 95% CI, 9.1% to 28.9%]), and NPV (prostate cancer: 59.3% vs 25.0% [difference, 34.3%; 95% CI, 10.9% to 57.6%]; melanoma: 80.8% vs 60.5% [difference, 20.3%; 95% CI, 10.0% to 30.7%]). For the ACMG genes, the sensitivity of the 2 methods was not significantly different in the prostate cancer cohort (94.9% vs 90.6% [difference, 4.3%; 95% CI, -2.3% to 10.9%]), but the deep learning method had a higher sensitivity in the melanoma cohort (71.6% vs 53.7% [difference, 17.9%; 95% CI, 1.82% to 34.0%]). The deep learning method had higher sensitivity in the mendelian genes (prostate cancer: 99.7% vs 95.1% [difference, 4.6%; 95% CI, 3.0% to 6.3%]; melanoma: 91.7% vs 86.2% [difference, 5.5%; 95% CI, 2.2% to 8.8%]). Conclusions and Relevance: Among a convenience sample of 2 independent cohorts of patients with prostate cancer and melanoma, germline genetic testing using deep learning, compared with the current standard genetic testing method, was associated with higher sensitivity and specificity for detection of pathogenic variants. Further research is needed to understand the relevance of these findings with regard to clinical outcomes.

Associations between the LEP -2548G/A Promoter and Baseline Weight and between LEPR Gln223Arg and Lys656Asn Variants and Change in BMI z Scores in Arab Children and Adolescents Treated with Risperidone.

Data on baseline (antipsychotics-naïve) age, weight, and height, and change in these at 3 subsequent follow-up time points up to 313.6 days (95% CI 303.5-323.7) were collected from 181 risperidone-treated children and adolescents (mean age 12.58 years, SD 4.99, range 2.17-17.7) attending a pediatric neurology clinic in Saudi Arabia. Owing to differences in genotypic distributions in the subsamples, results are reported for the white Arab population (n = 144). Age- and gender-normed body mass index (BMI)-standardized z scores (BMI z) were calculated (LMSgrowth program). Linear regression was performed for baseline weight and BMI z, while change in BMI z was assessed using random effects ordered logistic regression. The following single nucleotide polymorphisms (SNPs) were analyzed: rs7799039 in the LEP promoter, rs1805094 (previously rs8179183), rs1137100 and rs1137101 in the LEPR, and rs1414334 in HTR2C. We found a nominally significant association between rs7799309 and baseline weight, adjusting for height, age, gender, and diagnosis (A/G, p = 0.035, ß = -3.62 vs. G/G). The rs1137101 (G/G, p = 0.018, odds ratio [OR] = 4.13 vs. A/A) and rs1805094 C allele carriers (p = 0.019, OR = 0.51) showed nominally significant associations with change in BMI z categories. Our data support and replicate previous relevant associations for these variants (including with weight gain when on risperidone), whilst being the first report of such associations in patients of Arab ethnicity.

The self-limiting nature of statin-induced rhabdomyolysis.

Statins have come to the forefront of treatments for hyperlipidemias, coronary artery diseases and strokes. They have been shown to cause myotoxicity and rhabdomyolysis. In most cases, rhabdomyolysis is self-limiting and needs supportive therapy. Two cases of statin-induced rhabdomyolysis are reported emphasizing the definition, risk factors, clinical features and the self-limiting nature of the disorder.

Cerebral palsy in Saudi children.

OBJECTIVE: To describe the clinical profile, and identify its risk factors, of cerebral palsy (CP) as seen in a cohort of consecutive Saudi children aged between one and 3 years of age prospectively over a one-year period. METHODS: Saudi children aged 1-3 years with CP (diagnosis based on specified criteria) were selected from children presenting to the Neurology service at the King Fahd Hospital of the University, Al-Khobar, Kingdom of Saudi Arabia with delayed milestones, seizures, mental retardation and difficulty with walking and evaluated at 3-monthly intervals for one year from January to December 2000. Information on gestation duration, labor and delivery, birth weight and the medical history of the mothers was obtained. Cranial computerized tomography and electroencephalography were carried out in addition to baseline investigations (toxoplasmosis, other, rubella, cytomegalovirus, and herpes simplex virus serology, serum lactate, pyruvate, amino acid screen, thyroid function tests, and chromosome analysis). Somatosensory, molecular genetics and muscle biopsy for histopathologic and histochemical studies were not performed in any of the patients. RESULTS: One hundred and eighty-seven children with CP were seen during the study period: 109 males (mean age 20.3 +/- 8.69 months); 78 females (mean age 20.6 +/- 8.55 months). Seventy-three had microcephaly (<5th percentile) with a mean head circumference of 44.5 +/- 3.69 cms for males and 43.0 +/- 4.16 for females. The main symptoms were inability to walk independently (54%), delayed speech (52%) and seizures (45%). The main neurologic features were motor weakness (85%), spasticity (60%), language dysfunction (42%), mental retardation (31%) and head lag (30%). A history of previous CP in the family was obtained in 8 patients (4%) but none of them had other features of hereditary spastic paraplegia. Electroencephalography abnormalities, present in 113 (73%) were more frequent in those without seizures than with seizures. Cranial computerized tomography abnormalities were mainly cerebral atrophy (60%) and hydrocephalus (53.7%). Twenty-five percent were from twin pregnancies; 56 (34%) were of low birth weight, 20% were pre-term deliveries, birth asphyxia was present in 165 and breech presentation was encountered in 8%. CONCLUSION: The main risk factors identified were twin pregnancy, pre-term delivery, prolonged labor, low birth weight and a history of previous CP in the family. Our findings suggest that improved maternal and childcare particularly in the ante and perinatal periods may reduce the incidence of CP in this environment.

Newly diagnosed seizures in adults.

OBJECTIVE: To study the clinical, electroencephalographic (EEG) and computed tomography (CT) profile in a hospital population of over 18-years adult patients with newly diagnosed recurrent seizures. METHODS: The clinical profiles obtained from history including detailed description of the seizures, examination, EEG and CT findings were recorded prospectively for all over-18 patients who were referred to the electrodiagnostic service at King Fahd Hospital of the University, Al-Khobar, Eastern Province, Kingdom of Saudi Arabia from January 1, 1996 to December 31, 1997. The data was entered into a standard database file and analyzed using a personal computer. RESULTS: Seventy-three patients (43 males, 30 females, mean age 32.3 years) with newly diagnosed recurrent seizures were studied. A positive family history of seizures was found in 12.3%. The main seizure types were partial in 27 (37%), partial with secondary generalization in 22 (30.1%) and generalized in 24 (32.9%). The types of epileptic syndromes included localization-related 34 (46.6%), generalized 24 (32.9%) and undetermined 15 (20.5%). The EEG was abnormal in 45 (61.6%) with epileptiform activity, focal in 22 (48.9%), generalized in 11 (24.4%) and non-epileptiform activity in 12 (26.7%). The cranial CT findings were normal in 44 patients (60.3%) and abnormal in 29 (39.7%) patients, with focal lesions in 19 (65.5%) and generalized cerebral atrophy in 10 (34.5%). CONCLUSION: Our results showed that partial and partial with secondary generalization seizures are the most frequent seizure type and the most common epileptic syndrome was the localization-related type in this age group. These results are comparable to previous population- and hospital-based western reports.

Research and research activities in a university in Eastern Saudi Arabia.

OBJECTIVES: The purpose of the present study was to obtain the views of faculty members regarding various aspects of scientific research, which is one of the essential functions of a University. METHODS: A cross-sectional study was conducted in the College of Medicine, King Faisal University, Dammam, Kingdom of Saudi Arabia, between January and June 2001, using a standardized questionnaire to obtain the views of faculty members in both basic and clinical departments on issues related to scientific research. The questionnaire consisted of 41 items and the responses were assessed on a 5 point scale. The variables included specified objectives for research by administration, quality of research, process of application for funding, available facilities for research, constraints to meaningful scientific research and mechanisms that would enhance its quality. RESULTS: The response rate was 67% (74 of the total available 110): Professors 22, Associate Professors 27, Assistant Professors 23 and Lecturers 2 in 24 departments (6 basic sciences, 18 clinical sciences). The number of completed research projects was judged inadequately by 50 (68%), and 31 (42%) thought the quality could be improved upon. The process of the application for funding was cumbersome. The major identified constraints were inadequate infrastructure, additional administrative duties (89%) and teaching schedule overload (82%). The major strategies suggested to enhance the quality of research included simplifying the process for application for research (approval and funding), provision of defined quality time for faculty members to engage in research and the establishment of adequate support and infrastructure facilities. CONCLUSIONS: Most faculty members aspire for a higher quality of biomedical research. The following were identified strategies to improve research goals and quality: Provision of starting seedling packages for new faculty members, simplifying research application processes, establishing efficient and adequate infrastructures, and providing protected research time.

Did the national campaign for poliomyelitis vaccination achieve its objectives.

Full text is available as a scanned copy of the original print version.

Undergraduate Curriculum Reform in Saudi Medical Schools, needed or not?

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